{"doi":"10.1210/endocr/bqaf089","title":"Role of Branched-Chain Amino Acid Catabolism in the Regulation of Adipocyte Metabolism","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Adipocyte metabolism critically regulates systemic energy homeostasis, and its dysfunction contributes to obesity pathogenesis. Notably, elevated circulating branched-chain amino acid (BCAA) levels and impaired adipose tissue BCAA catabolism have been observed in both animal models and humans with obesity; however, the mechanisms underlying BCAA metabolism’s regulation of adipocyte function remain incompletely understood. This review synthesizes recent advances in the roles of BCAA catabolic enzymes, their metabolites, and BCAAs themselves in modulating adipocyte metabolism, encompassing adipogenesis, lipid metabolism, and thermogenesis. Emerging evidence reveals that BCAA catabolism influences adipocyte metabolism through multiple pathways: by utilizing BCAAs as an energy substrate, and modulating signaling cascades via metabolites and unidentified mechanisms. Importantly, adipocyte BCAA catabolism directly impacts systemic BCAA clearance and plasma BCAA concentrations. Dietary interventions involving BCAA supplementation, restriction, or deprivation demonstrate diverse metabolic effects on adipocytes, mediated through key nutrient-sensing pathways including mammalian target of rapamycin complex 1 (mTORC1) and general control nonderepressible kinase 2 (GCN2)/activating transcription factor 4 (ATF4) signaling. We further discuss translational implications, evaluating therapeutic strategies targeting BCAA catabolism or dietary BCAA manipulation for obesity management. This review advances our understanding of amino acid metabolism’s contribution to adipocyte function and obesity development.</jats:p>","journal":"Endocrinology","year":2025,"id":634560,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":215474,"name":"Feifan Guo","orcid":"0000-0003-3137-9781","position":1,"is_corresponding":false},{"id":655820,"name":"Fei Xiao","orcid":"0000-0003-2054-901X","position":2,"is_corresponding":false},{"id":1645804,"name":"Haizhou Jiang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Role of Branched-Chain Amino Acid Catabolism in the Regulation of Adipocyte Metabolism","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Adipocyte metabolism critically regulates systemic energy homeostasis, and its dysfunction contributes to obesity pathogenesis. Notably, elevated circulating branched-chain amino acid (BCAA) levels and impaired adipose tissue BCAA catabolism have been observed in both animal models and humans with obesity; however, the mechanisms underlying BCAA metabolism’s regulation of adipocyte function remain incompletely understood. This review synthesizes recent advances in the roles of BCAA catabolic enzymes, their metabolites, and BCAAs themselves in modulating adipocyte metabolism, encompassing adipogenesis, lipid metabolism, and thermogenesis. Emerging evidence reveals that BCAA catabolism influences adipocyte metabolism through multiple pathways: by utilizing BCAAs as an energy substrate, and modulating signaling cascades via metabolites and unidentified mechanisms. Importantly, adipocyte BCAA catabolism directly impacts systemic BCAA clearance and plasma BCAA concentrations. Dietary interventions involving BCAA supplementation, restriction, or deprivation demonstrate diverse metabolic effects on adipocytes, mediated through key nutrient-sensing pathways including mammalian target of rapamycin complex 1 (mTORC1) and general control nonderepressible kinase 2 (GCN2)/activating transcription factor 4 (ATF4) signaling. We further discuss translational implications, evaluating therapeutic strategies targeting BCAA catabolism or dietary BCAA manipulation for obesity management. This review advances our understanding of amino acid metabolism’s contribution to adipocyte function and obesity development.</jats:p>","is_dataset_classified":null,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40338053","pmcid":null,"openalex_id":"https://openalex.org/W4410210342","authors":[],"funders":[{"funder_name":"National Natural Science Foundation","grant_id":"82430030","title":null},{"funder_name":"National Natural Science Foundation","grant_id":"92357304","title":null},{"funder_name":"National Natural Science Foundation","grant_id":"82270905","title":null},{"funder_name":"National Natural Science Foundation","grant_id":"82401017","title":null},{"funder_name":"National Natural Science Foundation","grant_id":"82370811","title":null},{"funder_name":"National Natural Science Foundation","grant_id":"82300939","title":null},{"funder_name":"National Natural Science Foundation","grant_id":"82300940","title":null},{"funder_name":"National Key R&D Program of China","grant_id":"2018YFA0800600","title":null},{"funder_name":"Postdoctoral Fellowship Program of CPSF","grant_id":"GZC20230478","title":null},{"funder_name":"Postdoctoral Fellowship Program of CPSF","grant_id":"GZC20230479","title":null},{"funder_name":"China Postdoctoral Science Foundation","grant_id":"2024T170167","title":null},{"funder_name":"China Postdoctoral Science Foundation","grant_id":"2023M740695","title":null},{"funder_name":"Sanofi-Aventis SIBS scholarship","grant_id":"","title":null},{"funder_name":"Youth Innovation Promotion Association of CAS","grant_id":"","title":null},{"funder_name":"Shanghai Leading Talent Program","grant_id":"","title":null},{"funder_name":"Shanghai Rising Star Program","grant_id":"","title":null},{"funder_name":"Shanghai Leading Talent Program","grant_id":"","title":null},{"funder_name":"Youth Innovation Promotion Association of CAS","grant_id":"","title":null},{"funder_name":"Shanghai Rising Star Program","grant_id":"","title":null},{"funder_name":"Sanofi-Aventis SIBS scholarship","grant_id":"","title":null}],"total_grants":20,"fwci":4.4696,"citation_percentile":0.94793629,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":4}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/endo/advance-article-pdf/doi/10.1210/endocr/bqaf089/63126235/bqaf089.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/endo/article-pdf/166/7/bqaf089/63126235/bqaf089.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/endocr/bqaf089","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40338053","host_type":"repository"}],"fields_of_study":["Adipose Tissue and Metabolism","Metabolomics and Mass Spectrometry Studies","Adipokines, Inflammation, and Metabolic Diseases","Amino Acids, Branched-Chain","Humans","Animals","Adipocytes","Obesity","Adipogenesis","Lipid Metabolism","Signal Transduction","Energy Metabolism","Thermogenesis"],"mesh_terms":["Amino Acids, Branched-Chain","Animals","Energy Metabolism","Humans","Obesity","Signal Transduction","Adipocytes","Thermogenesis","Adipogenesis","Lipid Metabolism"],"keywords":["Catabolism","Adipocyte","Endocrinology","Internal medicine","Biology","mTORC1","Adipose tissue","Adipogenesis","Metabolism","Lipid metabolism","Energy homeostasis","Biochemistry","Signal transduction","PI3K/AKT/mTOR pathway","Medicine","Obesity","Thermogenesis","Branched-chain Amino Acids"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:49:48.513189Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}